• Klíčová slova
• β-adrenergní receptory, základní srdeční parametry a jejich biorytmy,
• MeSH
• adenylátcyklasy metabolismus   MeSH
• autonomní nervový systém MeSH
• beta-adrenergní receptory genetika   MeSH
• cykly aktivity MeSH
• financování organizované MeSH
• genový knockout MeSH
• myši knockoutované MeSH
• myši MeSH
• receptor muskarinový M2 genetika   nedostatek   MeSH
• regulace genové exprese genetika   MeSH
• srdce - funkce komor genetika   MeSH
• srdeční frekvence genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH

Although physiological responses to chronic hypoxia, including pulmonary hypertension and right ventricular hypertrophy, have been well described, the molecular mechanisms involved in cardiopulmonary adaptations are still not fully understood. We hypothesize that adaptive responses to chronic hypoxia are the result of altered transcriptional regulations in the right and left ventricles. Here we report results from the gene expression profiling of adaptive responses in a chronically hypoxic heart. Of 11 analyzed candidate genes, the expression of seven and four genes, respectively, was significantly altered in the right ventricle of hypoxic male and female mice. In the transcriptional profile of the left ventricle, we identified a single expression change in hypoxic males (Vegfa gene). To directly test the role of HIF1, we analyzed the expression profile in Hif1a partially deficient mice exposed to moderate hypoxia. Our data showed that Hif1a partial deficiency significantly altered transcriptional profiles of analyzed genes in hypoxic hearts. The expression changes were only detected in two genes in the right ventricle of Hif1a(+/-) males and in one gene in the right ventricle of Hif1a(+/-) females. First, our results suggest that hypoxia mainly affects adaptive expression profiles in the right ventricle and that each ventricle can respond independently. Second, our findings indicate that HIF1a plays an important role in adaptive cardiopulmonary responses and the dysfunction of HIF1 pathways considerably affects transcriptional regulation in the heart. Third, our data reveal significant differences between males and females in cardiac adaptive responses to hypoxia and indicate the necessity of optimizing diagnostic and therapeutic procedures in clinical practice, with respect to sex.

• MeSH
• časové faktory MeSH
• chronická nemoc MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa nedostatek   genetika   metabolismus   MeSH
• fyziologická adaptace MeSH
• genetická transkripce MeSH
• hematokrit MeSH
• hypoxie genetika   metabolismus   patofyziologie   MeSH
• kardiomegalie genetika   metabolismus   patofyziologie   MeSH
• krevní tlak MeSH
• messenger RNA metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• plicní hypertenze genetika   metabolismus   patofyziologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulace genové exprese MeSH
• sexuální faktory MeSH
• srdce - funkce komor genetika   MeSH
• srdeční komory metabolismus   patofyziologie   MeSH
• stanovení celkové genové exprese metody   MeSH
• tělesná hmotnost MeSH
• vaskulární endoteliální růstový faktor A genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

This study evaluated right ventricular (RV) and left ventricular (LV) diastolic tolerance to afterload and SERCA2a, phospholamban and sodium-calcium exchanger (NCX) gene expression in Wistar rats. Time constant ??and end diastolic pressure-dimension relation (EDPDR) were analyzed in response to progressive RV or LV afterload elevations, induced by beat-to-beat pulmonary trunk or aortic root constrictions, respectively. Afterload elevations decreased LV-?, but increased RV-?. Whereas LV-? analyzed the major course of pressure fall, RV-? only assessed the last fourth. Furthermore, RV afterload elevations progressively upward shifted RV EDPDR, whilst LV afterload elevations did not change LV-EDPDR. SERCA2a and phospholamban mRNA were similar in both ventricles. NCX-mRNA was almost 50 % lower in RV than in LV. Left ventricular afterload elevations, therefore, accelerated the pressure fall and did not induce diastolic dysfunction, indicating high LV diastolic tolerance to afterload. On the contrary, RV afterload elevations decelerated the late RV pressure fall and induced diastolic dysfunction, indicating small RV diastolic tolerance to afterload. These results support previous findings relating NCX with late Ca2+ reuptake, late relaxation and diastolic dysfunction.

• MeSH
• diastola fyziologie   genetika   MeSH
• exprese genu genetika   MeSH
• financování vládou MeSH
• hemodynamika fyziologie   genetika   MeSH
• interpretace statistických dat MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   využití   MeSH
• potkani Wistar fyziologie   genetika   MeSH
• pumpa pro výměnu sodíku a vápníku genetika   MeSH
• srdce - funkce komor fyziologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH